The purpose of the proposed study is to define by biochemical, functional and structural methods the mechanistic basis of the intraneutrophilic microbicidal defect in the canine qranulocytopathy syndrome (CGS). The clinical disease is affected animals, closely resembles the syndrome observed in human neutrophil dysfunction disorders, and is characterized by recurrent life-threatening infections and a greatly shortened life span. Complete genetic, clinical, and laboratory studies indicate the CGS is a genetically determined defect in host resistance to infection that is inherited as an autosomal recessive trait, and that although similar, the condition is uniquely different from any other documented human and animal host defense failure syndrome. Because the CGS provides previously unavailable opportunities for assessing the relative role of factors involved in the microbicidal event it appears that as a model of neutrophil dysfunction syndromes it may be a very valuable research resource. A series of studies are proposed which are designed to delineate the pathogenetic mechanism(s) responsible for the increased susceptibility of CGS affected dogs to infections. Although the efficacy of various different cellular and noncellular host defense factors will be evaluated, primary emphasis will be devoted to a metabolic, functional, and structural characterization of the neutrophil. The proposed metabolic studies are modeled after those which have been used to investigate both oxidative and nonoxidative bactericidal mechanisms of polymorphonuclear leukocytes in other mammalian species. These investigations will provide significant data about host defense mechanisms, cell function, and cell physiology and will, therefore, contribute to current knowledge of the structural and biochemical basis of the microbicidal event. Because of the unique nature of the CGS it could play a major role in confirmation of current theories and/or the development of new theories about the microbicidal event in polymorphonuclear leukocytes.